Endovascular therapy in acute ischaemic stroke with large infarction with matched or mismatched clinical-radiological severities: a post-hoc analysis of the ANGEL-ASPECT trial.

Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3-5 or infarct core volume 70-100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18-2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06-2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

Environmental factors affecting the risk of generalization for ocular-onset myasthenia gravis: a nationwide cohort study.

BACKGROUND: The environmental effects on the prognosis of ocular myasthenia gravis (OMG) remain largely unexplored. AIM: To investigate the association between specific environmental factors and the generalization of OMG. DESIGN: The cohort study was conducted in China based on a nationwide multicenter database. METHODS: Adult patients with OMG at onset, who were followed up for at least 2 years until May 2022, were included. We collected data on demographic and clinical factors, as well as environmental factors, including latitude, socioeconomic status (per capita disposable income [PDI] at provincial level and education) and smoking. The study outcome was the time to the development of generalized myasthenia gravis (GMG). Cox models were employed to examine the association between environmental exposures and generalization. Restricted cubic spline was used to model the association of latitude with generalization risk. RESULTS: A total of 1396 participants were included. During a median follow-up of 5.15 (interquartile range [IQR] 3.37-9.03) years, 735 patients developed GMG within a median of 5.69 (IQR 1.10-15.66) years. Latitude of 20-50°N showed a U-shaped relation with generalization risk, with the lowest risk at around 30°N; both higher and lower latitudes were associated with the increased risk (P for non-linearity <0.001). Living in areas with lower PDI had 1.28-2.11 times higher risk of generalization. No significant association was observed with education or smoking. CONCLUSIONS: Latitude and provincial-level PDI were associated with the generalization of OMG in China. Further studies are warranted to validate our findings and investigate their potential applications in clinical practice and health policy.

Cost-effectiveness of endovascular therapy for acute ischemic stroke with large infarct in China.

BACKGROUND: Endovascular therapy administered within 24 hours has been shown to improve outcomes for patients with acute ischemic stroke with large infarction, but the data on its cost-effectiveness are limited. OBJECTIVE: To evaluate the cost-effectiveness of endovascular therapy for acute ischemic stroke with large infarction in China, the largest low- and middle-income country. METHODS: A short-term decision tree model and a long-term Markov model were used to analyze the cost-effectiveness of endovascular therapy for patients with acute ischemic stroke with large infarction. Outcomes, transition probability, and cost data were obtained from a recent clinical trial and published literature. The benefit of endovascular therapy was assessed by the cost per quality-adjusted life-years (QALYs) gained in the short and long term. Deterministic one-way and probabilistic sensitivity analyses were performed to assess the robustness of the results. RESULTS: Compared with medical management alone, endovascular therapy for acute ischemic stroke with large infarction was found to be cost-effective from the fourth year onward and during a lifetime. In the long term, endovascular therapy yielded a lifetime gain of 1.33 QALYs at an additional cost of ¥73 900 (US$ 11 400), resulting in an incremental cost of ¥55 500 (US$ 8530) per QALY gained. Probabilistic sensitivity analysis showed that endovascular therapy was cost-effective in 99.5% of the simulation runs at a willingness-to-pay threshold of ¥243 000 (3 × gross domestic product per capita of China in 2021) per QALY gained. CONCLUSIONS: Endovascular therapy for acute ischemic stroke with large infarction could be cost-effective in China.

Predictors of parenchymal hemorrhage after endovascular treatment in acute ischemic stroke: data from ANGEL-ACT Registry.

BACKGROUND: Parenchymal hemorrhage (PH) is a troublesome complication after endovascular treatment (EVT). OBJECTIVE: To investigate the incidence, independent predictors, and clinical impact of PH after EVT in patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO). METHODS: Subjects were selected from the ANGEL-ACT Registry. PH was diagnosed according to the European Collaborative Acute Stroke Study classification. Logistic regression analyses were performed to determine the independent predictors of PH, as well as the association between PH and 90-day functional outcome assessed by modified Rankin Scale (mRS) score. RESULTS: Of the 1227 enrolled patients, 147 (12.0%) were diagnosed with PH within 12-36 hours after EVT. On multivariable analysis, low admission Alberta Stroke Program Early CT score (ASPECTS)(adjusted OR (aOR)=1.13, 95% CI 1.02 to 1.26, p=0.020), serum glucose >7 mmol/L (aOR=1.82, 95% CI 1.16 to 2.84, p=0.009), and neutrophil-to-lymphocyte ratio (NLR; aOR=1.05, 95% CI 1.02 to 1.09, p=0.005) were associated with a high risk of PH, while underlying intracranial atherosclerotic stenosis (ICAS; aOR=0.42, 95% CI 0.22 to 0.81, p=0.009) and intracranial angioplasty/stenting (aOR=0.37, 95% CI 0.15 to 0.93, p=0.035) were associated with a low risk of PH. Furthermore, patients with PH were associated with a shift towards to worse functional outcome (mRS score 4 vs 3, adjusted common OR (acOR)=2.27, 95% CI 1.53 to 3.38, p<0.001). CONCLUSIONS: In Chinese patients with AIS caused by anterior circulation LVO, the risk of PH was positively associated with low admission ASPECTS, serum glucose >7 mmol/L, and NLR, but negatively related to underlying ICAS and intracranial angioplasty/stenting. TRIAL REGISTRATION NUMBER: NCT03370939.

Unexplained early neurological deterioration after endovascular treatment for acute large vessel occlusion: incidence, predictors, and clinical impact: Data from ANGEL-ACT registry.

BACKGROUND: Early neurological deterioration (END) may occur in some patients with acute large vessel occlusion (LVO) undergoing endovascular treatment (EVT). Despite several clear causes of END, such as symptomatic intracranial hemorrhage, failure of recanalization, and intraprocedure complications, a particular END, termed unexplained END (ENDunexplained), exists. We aimed to investigate the incidence, independent predictors, and clinical impact of ENDunexplained after EVT in patients with acute LVO. METHODS: Subjects were selected from the ANGEL-ACT registry. ENDunexplained was defined as ≥4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score between baseline and 24 hours after EVT, without the causes listed above. Logistic regression analyses were performed to determine the independent predictors of ENDunexplained, as well as the association between ENDunexplained and 90-day outcomes assessed by modified Rankin Scale (mRS) score. RESULTS: Among the 1557 enrolled patients, the incidence of ENDunexplained was 4.3% (67/1557). Admission NIHSS ≤8 (OR=6.88, 95% CI 3.86 to 12.26, p<0.001), general anesthesia (OR=3.15, 95% CI 1.81 to 5.48, p<0.001), admission neutrophil to lymphocyte ratio >5 (OR=2.82, 95% CI 1.61 to 4.94, p<0.001), and number of EVT attempts >3 (OR=2.11, 95% CI 1.14 to 3.89, p=0.018) were associated independently with a high risk of ENDunexplained. Furthermore, patients with ENDunexplained were associated with a shift toward worse 90-day outcomes (mRS 5 vs 3, common OR=5.24, 95% CI 3.22 to 8.52, p<0.001). CONCLUSIONS: ENDunexplained associated with poor 90day outcomes occurred in 4.3% of patients with acute LVO undergoing EVT. Several independent predictors of ENDunexplained were identified in this study, which should be considered in daily practice to improve acute LVO management. CLINICAL TRIAL REGISTRATION: http://wwwclinicaltrialsgov NCT03370939.

Non-contrast head CT alone for thrombectomy in acute ischemic stroke: analysis of the ANGEL-ACT registry.

BACKGROUD: The goal of this study was to determine if the choice of imaging paradigm performed in the emergency department influences the procedural or clinical outcomes after mechanical thrombectomy (MT). METHODS: This is a retrospective comparative outcome study which was conducted from the ANGEL-ACT registry. Comparisons were made between baseline characteristics and clinical outcomes of patients with acute ischemic stroke undergoing MT with non-contrast head computed tomography (NCHCT) alone versus patients undergoing NCHCT plus non-invasive vessel imaging (NVI) (including CT angiography (with or without CT perfusion) and magnetic resonance angiography). The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included change in mRS score from baseline to 90 days, the proportions of mRS 0-1, 0-2, and 0-3, and dramatic clinical improvement at 24 hours. The safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH, and mortality within 90 days. RESULTS: A total of 894 patients met the inclusion criteria; 476 (53%) underwent NCHCT alone and 418 (47%) underwent NCHCT + NVI. In the NCHCT alone group, the door-to-reperfusion time was shorter by 47 min compared with the NCHCT + NVI group (219 vs 266 min, P<0.001). Patients in the NCHCT alone group showed a smaller increase in baseline mRS score at 90 days (median 3 vs 2 points; P=0.004) after adjustment. There were no significant differences between groups in the remaining clinical outcomes. CONCLUSIONS: In patients selected for MT using NCHCT alone versus NCHCT + NVI, there were improved procedural outcomes and smaller increases in baseline mRS scores at 90 days.

Myocardial Infarction Is Associated With Increased Stroke Severity, In-Hospital Mortality, and Complications: Insights From China Stroke Center Alliance Registries.

Background Prior studies have shown an increased risk of ischemic stroke (IS) after myocardial infarction (MI); however, there are limited studies concerning the characteristics, in-hospital mortality, and complications of patients with IS with a medical history of MI. We hypothesized that patients with IS with a medical history of MI may experience more severe strokes and have a higher risk of in-hospital mortality and complications than patients with IS without a medical history of MI. Methods and Results Consecutive in-hospital data were extracted from the China Stroke Center Alliance database from August 2015 to July 2019. Patient characteristics, hospital tests, in-hospital mortality, and complications were analyzed and compared in patients with IS with or without a history of MI. Of 893 429 patients with IS, we identified 81 646 (9.1%) patients with a history of MI (MI group). Compared with patients with IS without MI, MI group patients were older, had a lower prevalence of current smoking, had a higher prevalence of a relative medical history, and took more medications before admission. Compared with the group with IS without MI, the MI group had a higher National Institute of Health Stroke Scale score after onset (4.0 versus 3.0; Hodges-Lehmann estimator, 22.5) and a higher proportion of severe strokes (National Institute of Health Stroke Scale score ≥15) (7.1% versus 4.4%; absolute standardized difference=11.6%). In the fully adjusted models, the risk of in-hospital mortality was higher in the MI group (odds ratio [OR], 1.74; 95% CI, 1.57-1.92; P<0.0001). MI group patients also had a higher risk of complications, including urinary tract infection (OR, 1.28; 95% CI, 1.2-1.36; P<0.0001), gastrointestinal bleeding (OR, 1.29; 95% CI, 1.19-1.39; P<0.0001), pneumonia (OR, 1.24; 95% CI, 1.21-1.28; P<0.0001), depression (OR, 1.33; 95% CI, 1.24-1.42; P<0.0001), seizure (OR, 1.35; 95% CI, 1.22-1.49; P<0.0001), atrial fibrillation (OR, 1.78; 95% CI, 1.71-1.86; P<0.0001), and cardiac or respiratory arrest (OR, 1.98; 95% CI, 1.78-2.2; P<0.0001). Conclusions Patients with IS with a medical history of MI have an increased risk of severe stroke, in-hospital mortality, and complications. Studies exploring the underlying mechanisms are needed to improve and tailor stroke treatment strategies.

Overexpression of miR-224-3p alleviates apoptosis from cerebral ischemia reperfusion injury by targeting FIP200.

AIMS: In previous studies, numerous differential microRNAs (miRNAs) in cerebral ischemic/reperfusion (I/R) injury were identified using the miRNA microarray analysis. However, the relationship between miRNA and cerebral I/R injury remains largely unknown. In this study, we investigated the function and explored the possible mechanism of miR-224-3p in cerebral I/R injury. METHODS: Oxygen glucose deprivation model in N2a cells were used to perform the cerebral I/R injury in vitro. Trypan blue staining, reactive oxygen species (ROS) production, and caspase-3 were measured to evaluate the function of miR-224-3p. RESULTS: Overexpression of miR-224-3p alleviated the apoptosis induced by oxygen glucose deprivation (OGD) and cleaved caspase-3 was significantly reduced. We further provided the possible mechanism that miR-224-3p may protect cells from cerebral I/R injury by targeting FAK family-interacting protein (FIP200). Further rescue experiment proved that overexpression of FIP200 partially blocked the effect of miR-224-3p. CONCLUSIONS: We evaluated the function and mechanism of miR-224-3p in ischemic brain injury. miR-224-3p may serve as a potential target for new therapeutic intervention.

Encephalopathy associated with propofol infusion syndrome: A case report.

INTRODUCTION: Propofol infusion syndrome (PRIS) is a rare but potentially fatal complication of propofol infusion. It is clinically characterized by metabolic acidosis, refractory bradycardia, rhabdomyolysis, renal failure, hyperlipidemia, and hepatomegaly. Brain lesion was only reported once in a pediatric patient. We present the 1st adult case with colon polyp and cancer who was diagnosed with PRIS. Her brain magnetic resonance imaging (MRI) and computed tomography (CT) scans reveal prominent bilateral brain lesions, matching with the proposed pathophysiologic mechanism of the syndrome. The patient received prompt acidosis correction and cardiorespiratory support. At last, she died from refractory circulatory failure. CONCLUSION: It may be necessary to order a prompt neuroimaging examination in patients suspected with PRIS to judge whether brain lesions exist or not.

SCL20A2 mutation presenting with acute ischemic stroke: a case report.

BACKGROUND: Primary familial brain calcification (PFBC) is a rare disorder characterized by distinctive bilateral brain calcification and variable clinical presentations. However, cerebrovascular attack was rarely reported in PFBC patients. We here reported a SLC20A2 mutation patient presenting with acute ischemic stroke. CASE PRESENTATION: A 56 years old man was transferred to our hospital because of 6 days of melena and 3 days of somnolence, agitation and mood changes. Computed tomography (CT) scan showed symmetrical calcifications in bilateral basal ganglia, caudate nucleus, thalami, subcortical white matter and cerebellum, which is consistent with PFBC. Brain magnetic resonance imaging (MRI) revealed acute ischemic stroke in bilateral basal ganglia and periventricular regions. Mutational analysis identified a SLC20A2 gene mutation c.344C > T (p.Thr115Met) in exon 3. One of his daughters had also suffered from brain calcification. MR perfusion imaging revealed hypoperfusion in bilateral basal ganglia, prefrontal and temporal lobe. After treatment, he discharged with a favorable functional outcome but cognitive impairment. CONCLUSIONS: Ischemic stroke can occur in PFBC patients, which may be associated with hypoperfusion and calcification of arteries. And hypoperfusion in frontotemporal lobar may be related with their cognitive impairment.